Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25122 | 75589;75590;75591 | chr2:178570768;178570767;178570766 | chr2:179435495;179435494;179435493 |
| N2AB | 23481 | 70666;70667;70668 | chr2:178570768;178570767;178570766 | chr2:179435495;179435494;179435493 |
| N2A | 22554 | 67885;67886;67887 | chr2:178570768;178570767;178570766 | chr2:179435495;179435494;179435493 |
| N2B | 16057 | 48394;48395;48396 | chr2:178570768;178570767;178570766 | chr2:179435495;179435494;179435493 |
| Novex-1 | 16182 | 48769;48770;48771 | chr2:178570768;178570767;178570766 | chr2:179435495;179435494;179435493 |
| Novex-2 | 16249 | 48970;48971;48972 | chr2:178570768;178570767;178570766 | chr2:179435495;179435494;179435493 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/M | rs376821762  |
-0.321 | 0.999 | N | 0.532 | 0.296 | None | gnomAD-2.1.1 | 5.64E-05 | None | None | None | None | N | None | 0 | 8.69E-05 | None | 9.96E-05 | 0 | None | 3.27E-05 | None | 0 | 8.02E-05 | 0 |
| V/M | rs376821762 |
-0.321 | 0.999 | N | 0.532 | 0.296 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/M | rs376821762 |
-0.321 | 0.999 | N | 0.532 | 0.296 | None | gnomAD-4.0.0 | 8.61509E-05 | None | None | None | None | N | None | 0 | 6.66889E-05 | None | 3.37883E-05 | 0 | None | 0 | 0 | 1.11899E-04 | 1.09796E-05 | 1.60143E-05 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2014 | likely_benign | 0.2366 | benign | -1.241 | Destabilizing | 0.63 | D | 0.459 | neutral | N | 0.490011651 | None | None | N |
| V/C | 0.7061 | likely_pathogenic | 0.7717 | pathogenic | -0.716 | Destabilizing | 0.999 | D | 0.606 | neutral | None | None | None | None | N |
| V/D | 0.4784 | ambiguous | 0.5965 | pathogenic | -1.208 | Destabilizing | 0.975 | D | 0.713 | prob.delet. | None | None | None | None | N |
| V/E | 0.3366 | likely_benign | 0.4354 | ambiguous | -1.229 | Destabilizing | 0.967 | D | 0.625 | neutral | N | 0.481716311 | None | None | N |
| V/F | 0.1844 | likely_benign | 0.2255 | benign | -1.0 | Destabilizing | 0.987 | D | 0.621 | neutral | None | None | None | None | N |
| V/G | 0.3664 | ambiguous | 0.4362 | ambiguous | -1.518 | Destabilizing | 0.967 | D | 0.623 | neutral | N | 0.510143822 | None | None | N |
| V/H | 0.5453 | ambiguous | 0.6371 | pathogenic | -1.062 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | N |
| V/I | 0.0733 | likely_benign | 0.0731 | benign | -0.592 | Destabilizing | 0.818 | D | 0.461 | neutral | None | None | None | None | N |
| V/K | 0.3861 | ambiguous | 0.4863 | ambiguous | -1.183 | Destabilizing | 0.975 | D | 0.656 | neutral | None | None | None | None | N |
| V/L | 0.1647 | likely_benign | 0.1979 | benign | -0.592 | Destabilizing | 0.812 | D | 0.475 | neutral | N | 0.494748592 | None | None | N |
| V/M | 0.1317 | likely_benign | 0.1473 | benign | -0.426 | Destabilizing | 0.999 | D | 0.532 | neutral | N | 0.49550906 | None | None | N |
| V/N | 0.3236 | likely_benign | 0.3831 | ambiguous | -0.919 | Destabilizing | 0.975 | D | 0.72 | prob.delet. | None | None | None | None | N |
| V/P | 0.6574 | likely_pathogenic | 0.7424 | pathogenic | -0.774 | Destabilizing | 0.987 | D | 0.696 | prob.neutral | None | None | None | None | N |
| V/Q | 0.3435 | ambiguous | 0.424 | ambiguous | -1.102 | Destabilizing | 0.987 | D | 0.699 | prob.neutral | None | None | None | None | N |
| V/R | 0.3327 | likely_benign | 0.4238 | ambiguous | -0.61 | Destabilizing | 0.975 | D | 0.725 | prob.delet. | None | None | None | None | N |
| V/S | 0.239 | likely_benign | 0.2762 | benign | -1.337 | Destabilizing | 0.845 | D | 0.535 | neutral | None | None | None | None | N |
| V/T | 0.1287 | likely_benign | 0.1388 | benign | -1.258 | Destabilizing | 0.014 | N | 0.197 | neutral | None | None | None | None | N |
| V/W | 0.7669 | likely_pathogenic | 0.8499 | pathogenic | -1.197 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| V/Y | 0.5147 | ambiguous | 0.6124 | pathogenic | -0.915 | Destabilizing | 0.996 | D | 0.63 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.